MicroRNA-597 Suppresses Gastric Cancer Invasion and Progression via RUNX1 Targeting, an Effect Attenuated by the Long Non-Coding RNA KCNQ1OT1

Sandoval-Borquez, Alejandra; Olivares, Wilda; Carvajal, Francisco J.; Santoro, Pablo M.; Bizama, Carolina; Ávalos-Guajardo, Yáreni; Torres, Keila; Garrido, Marcelo; Norero, Enrique; Quest, Andrew F. G.; Corvalan, Alejandro H.

doi:10.3390/ijms27125368

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MicroRNA-597 Suppresses Gastric Cancer Invasion and Progression via RUNX1 Targeting, an Effect Attenuated by the Long Non-Coding RNA KCNQ1OT1

by

Alejandra Sandoval-Borquez

^1,2

,

Wilda Olivares

^1,3

,

Francisco J. Carvajal

^1,3

,

Pablo M. Santoro

^1,3

,

Carolina Bizama

^1,4,

Yáreni Ávalos-Guajardo

^1,4,

Keila Torres

^1,3

,

Marcelo Garrido

^3,†,‡,

Enrique Norero

⁵,

Andrew F. G. Quest

^6,7,8,9 and

Alejandro H. Corvalan

^1,3,*

¹

Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile

²

Medical Technology School, Faculty of Sciences, Pontificia Universidad Católica de Valparaíso, Valparaiso 2370363, Chile

³

Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330032, Chile

⁴

Department of Pathology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile

⁵

Esophagogastric Surgery Unit, Department of Digestive Surgery, Hospital Dr. Sotero del Rio, Santiago 8207257, Chile

⁶

Cellular Communication Laboratory, Faculty of Medicine, University of Chile, Santiago 8380453, Chile

⁷

⁷ Center for Studies on Exercise, Metabolism and Cancer (CEMC), Faculty of Medicine, University of Chile, Santiago 8380453, Chile

⁸

⁸ Nucleus of Biology and Genetics, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago 8389100, Chile

⁹

⁹ Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, University of Chile, Santiago 8389100, Chile

^*

Author to whom correspondence should be addressed.

^†

Current address: Hemato-Oncology Department, SAGA Clinical Trial Center, Av. Antonio Varas 517, Providencia, Santiago 7500653, Chile.

^‡

Current address: Indisa Clinic, Av. Santa María 1810, Providencia, Santiago 7520440, Chile.

Int. J. Mol. Sci. 2026, 27(12), 5368; https://doi.org/10.3390/ijms27125368 (registering DOI)

Submission received: 10 April 2026 / Revised: 11 June 2026 / Accepted: 11 June 2026 / Published: 14 June 2026

(This article belongs to the Special Issue The Role of Micro-RNA in Gastrointestinal Cancers—from Molecules to Novel Therapies)

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Abstract

Aberrant expression of multiple microRNAs has been reported in gastric cancer. In particular, microRNA-597 has been associated with poor survival rates but is not yet well characterized. Seventy-five clinical samples, four cell lines, and two patient-derived organoids were evaluated for the expression of microRNA-597 and its target genes. microRNA-597 was transiently transfected for analysis of cell migration, invasion, wound healing, colony formation, and cell viability, and its regulation by long non-coding RNAs was explored using the TCGA-STAD and LncBook tools. In clinical samples, low expression of microRNA-597 was associated with the intestinal subtype (p = 0.002) and stages III and IV (p = 0.048). All functional readouts were reduced after microRNA-597 transfection, including colony formation, in patient-derived organoids. Among target genes, RUNX1 was directly regulated by microRNA-597. Other cell invasion genes were dependent on RUNX1 as a hub for regulation. Analysis of the Intersection between long non-coding RNAs co-expressed with RUNX1 and those with the highest microRNA-597 prediction binding identified KCNQ1OT1 as the top transcript. Silencing of KCNQ1OT1 and co-expression in clinical samples suggest the existence of a KCNQ1OT1/microRNA-597/RUNX1 network. The results indicate that microRNA-597 directly suppresses RUNX1, while KCNQ1OT1 modulates this interaction. Our approach enabled the simultaneous analysis of dysregulation in three families of transcripts in gastric cancer progression.

Keywords: gastric cancer; KCNQ1OT1; microRNA-597; RUNX1; patient-derived organoids

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MDPI and ACS Style

Sandoval-Borquez, A.; Olivares, W.; Carvajal, F.J.; Santoro, P.M.; Bizama, C.; Ávalos-Guajardo, Y.; Torres, K.; Garrido, M.; Norero, E.; Quest, A.F.G.; et al. MicroRNA-597 Suppresses Gastric Cancer Invasion and Progression via RUNX1 Targeting, an Effect Attenuated by the Long Non-Coding RNA KCNQ1OT1. Int. J. Mol. Sci. 2026, 27, 5368. https://doi.org/10.3390/ijms27125368

AMA Style

Sandoval-Borquez A, Olivares W, Carvajal FJ, Santoro PM, Bizama C, Ávalos-Guajardo Y, Torres K, Garrido M, Norero E, Quest AFG, et al. MicroRNA-597 Suppresses Gastric Cancer Invasion and Progression via RUNX1 Targeting, an Effect Attenuated by the Long Non-Coding RNA KCNQ1OT1. International Journal of Molecular Sciences. 2026; 27(12):5368. https://doi.org/10.3390/ijms27125368

Chicago/Turabian Style

Sandoval-Borquez, Alejandra, Wilda Olivares, Francisco J. Carvajal, Pablo M. Santoro, Carolina Bizama, Yáreni Ávalos-Guajardo, Keila Torres, Marcelo Garrido, Enrique Norero, Andrew F. G. Quest, and et al. 2026. "MicroRNA-597 Suppresses Gastric Cancer Invasion and Progression via RUNX1 Targeting, an Effect Attenuated by the Long Non-Coding RNA KCNQ1OT1" International Journal of Molecular Sciences 27, no. 12: 5368. https://doi.org/10.3390/ijms27125368

APA Style

Sandoval-Borquez, A., Olivares, W., Carvajal, F. J., Santoro, P. M., Bizama, C., Ávalos-Guajardo, Y., Torres, K., Garrido, M., Norero, E., Quest, A. F. G., & Corvalan, A. H. (2026). MicroRNA-597 Suppresses Gastric Cancer Invasion and Progression via RUNX1 Targeting, an Effect Attenuated by the Long Non-Coding RNA KCNQ1OT1. International Journal of Molecular Sciences, 27(12), 5368. https://doi.org/10.3390/ijms27125368

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MicroRNA-597 Suppresses Gastric Cancer Invasion and Progression via RUNX1 Targeting, an Effect Attenuated by the Long Non-Coding RNA KCNQ1OT1

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